eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Thrush

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine

Updated: Jan 23, 2009

Introduction

Background

First described by the French pediatrician Francois Valleix in 1838, thrush is an infection of the buccal cavity by Candida albicans. The disease is typically limited to infants and neonates, patients on antibiotics or steroids, and patients with polyendocrine disorders or underlying immune dysfunction. Thrush may be the first sign of human immunodeficiency virus (HIV) infection; its appearance in advanced HIV indicates poor prognosis. Children on inhaled steroids also have increased incidence of oral candidiasis.

Pathophysiology

C albicans causes thrush when normal host immunity or normal host flora is disrupted. Overgrowth of yeast on the oral mucosa leads to desquamation of epithelial cells and accumulation of bacteria, keratin, and necrotic tissue. This debris combines to form a pseudomembrane, which may closely adhere to the mucosa. This membrane is usually not large but may rarely involve extensive areas of edema, ulceration, and necrosis of the underlying mucosa.

Affected neonates are typically colonized by C albicans during passage through the birth canal. Hence, the risk for thrush is increased when the mother has an active vaginal yeast infection. Other sources of transmission to neonates include colonized breasts (for breastfed infants), hands, and/or improperly cleaned bottle nipples. Kissing has also been implicated.

C albicans frequently and asymptomatically inhabits the GI tract of many children and adults, and the GI tract has been implicated as a reservoir for yeast contamination of the perineum. Thus, candidal diaper rash frequently occurs in conjunction with thrush.

Frequency

United States

As many as 37% of newborns may develop thrush during the first months of life.

International

Thrush is universal and is more common in poorly nourished populations.

Mortality/Morbidity

Thrush is usually a mild and self-limited illness, although it may cause discomfort sufficient to disrupt feeding in a newborn. Consider the possibility of an underlying immunodeficiency when thrush occurs after early infancy or without a reasonable explanation.

Sex

Thrush occurs equally in males and females.

Age

Thrush is rare during the first week of life. Incidence peaks around the fourth week of life; thrush is uncommon in infants older than 6-9 months. Thrush can occur, however, at any age in predisposed patients.

Clinical

History

• Parents of children with thrush usually notice a white coating in the child's mouth.
• Infants may have trouble feeding in severe cases.
• Medical history may include the following:
  • Recent antibiotic or steroid use may suggest a predisposing cause.
  • Diarrhea, rashes, failure to thrive, hepatosplenomegaly, or repeated infections suggest an underlying immunodeficiency.
• Maternal history may include the following:
  • Vaginal candidiasis is a source of perinatal exposure to infection.
  • HIV status may provide a clue to a predisposing factor.

Physical

• Lesions often start as tiny focal areas that enlarge to white patches on oral mucosae.
• When scraped with a tongue blade, lesions are difficult to remove and leave behind an inflamed base that may be painful and may bleed.
• Candidal infection in the diaper area may accompany thrush. Examine an infant with diaper dermatitis for oral lesions.¹
• Differentiate thrush from a coated tongue.
• Thorough physical examination is critical, especially for patients with recurrent thrush and for older children. Pay attention to the child's growth, rash distribution, lymphadenopathy, hepatosplenomegaly, and other potential sites of infection (eg, mucocutaneous candidiasis^2,3,4 ).

Causes

• Consider an underlying immune deficiency, especially in recurrent cases and in older infants.
• Systemic antibiotic use may disrupt the normal flora, promoting candidal overgrowth.
• Use of systemic and inhaled steroids is associated with increased incidence of oral thrush.

Differential Diagnoses

Other Problems to Be Considered

Milk curd
Foreign bodies

Workup

Laboratory Studies

• A relatively simple way to confirm the suspected diagnosis is to scrape the plaques with a tongue blade to reveal an inflamed and/or bleeding base.
• Plaques can be cultured, although cultures are rarely indicated. A simple Gram stain demonstrates large, gram-positive yeast.

Other Tests

• Diagnosis can be confirmed by simple histologic findings.

Histologic Findings

• Pseudohyphae and gram-positive yeast can be seen on Gram stain or with potassium hydroxide stain.

Treatment

Medical Care

Although some anecdotal reports indicate no treatment is necessary for otherwise healthy neonates, no published studies support this assertion.⁵

Consultations

In cases in which underlying immune dysfunction is suspected, consultation with an immunologist and infectious diseases specialist may be warranted for further evaluation.

Diet

No special diet is indicated.

Medication

Antifungal therapy generally hastens resolution of infection. The treatment of choice for thrush is oral nystatin suspension, although numerous antifungal agents are effective. Resistance to nystatin is rare, although the drug's contact killing makes it somewhat more difficult to use because it must be applied to all of the affected mucosal surfaces to be effective (unlike systemic therapies).

In older children and adults, antifungal medications should be swished around in the oral cavity and swallowed. Failure to do so may provide ineffective treatment for lesions in the posterior pharynx and esophagus. In younger patients, instruct parents to apply 1-2 mL of the solution to the inside of each cheek during each administration. Medication can also be directly applied to the lesions with a nonabsorbent swab or applicator. The best time to administer medication is between meals because this allows longer contact time.

Gentian violet solution should not be swallowed. Lozenges (troches) may be used if suspension preparations are unavailable.

These antifungal preparations have minimal adverse effects and few contraindications because they involve little or no systemic absorption. Aside from itraconazole, against which candidal resistance is increasing, other readily available antifungals are effective. If inability to adequately apply nystatin (or the oral cavity's normal flushing mechanisms) results in treatment failure, oral fluconazole or gentian violet are second-line agents.

Antifungal agents

The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Nystatin (Mycostatin, Nilstat, Nystex)

DOC for oral thrush. No significant absorption from the intact skin, GI tract, or vagina. Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.

Dosing

Adult

400,000-600,000 U PO; swish and swallow 4-5 times/d
Dissolve 1-2 (200,000-400,000 U) troches (lozenges) in mouth 4-5 times/d
Continue treatment until 48 h after symptoms disappear

Pediatric

Infants, young children: Apply 100,000-200,000 U PO susp to affected areas of mouth 3-5 times/d
Continue treatment until 48 h after symptoms disappear
Older children: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

No serious adverse effects; bitter taste, nausea, abdominal pain, diarrhea, urticaria

Amphotericin B (Fungizone Oral Suspension)

Produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Dosing

Adult

100-200 mg PO; swish and swallow qid

Pediatric

Apply 100-mg oral susp to affected areas of mouth qid

Interactions

Unlikely with PO administration because of poor absorption; may increase nephrotoxicity when used with aminoglycosides and possibly with cephalosporins; may increase methotrexate toxicity; increases curariform effect of curariform drugs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Minimal adverse effects expected with PO administration

Clotrimazole (Mycelex Troches)

Alters cell membrane. Very effective treatment in immunocompetent host. If susp not available (not available in the United States), troches (lozenges) can be used, but troche has been associated with elevated liver enzymes and GI adverse effects.

Dosing

Adult

10 mg troche dissolved PO 5 times/d

Pediatric

Infants: Not established
Older children: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

Miconazole oral gel (Daktar)

Not available in the United States. Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol; increases membrane permeability, causing nutrients to leak out, resulting in fungal cell death.

Dosing

Adult

Pediatric

Apply 25 mg to affected areas of mouth qid; exact PO topical dose not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Sensitivity or chemical irritation

Gentian violet

Although inexpensive, efficacious for thrush refractory to other therapies. Solution stains clothing and mucosa intensely, causing undesirable cosmetic effects.

Dosing

Adult

2% solution PO topically bid; treat until plaques clear

Pediatric

Infants: 3-4 gtt 0.5% solution PO topically qd pc
Children: 1% solution PO topically qd; treat until plaques clear

Interactions

None reported

Contraindications

Documented hypersensitivity; ulcerated areas; porphyria

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Esophagitis if swallowed; may burn skin; intense staining of mucosa may interfere with assessment of response

Fluconazole (Diflucan)

Azole antifungal with excellent bioavailability. Interferes with cell membrane and is eliminated via renal pathway.
Fungistatic activity. Synthetic PO antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

Dosing

Adult

200 mg PO qd on day 1; followed by 100 mg/d PO for 3-4 d; total of 5 d should be adequate

Pediatric

6 mg/kg/d PO qd

Interactions

Serum levels may increase with hydrochlorothiazide; levels may decrease with chronic coadministration of rifampin; coadministration may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; cyclosporine concentrations increases may occur when administered concurrently

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor closely if rash develops and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death), with underlying medical conditions (eg, AIDS, malignancy) and while taking multiple concomitant medications; not recommended for nursing mothers

Follow-up

Complications

• Very rarely, extensive tracheal and esophageal involvement in thrush may lead to dysphagia and respiratory distress in otherwise healthy hosts.
• Bronchopulmonary candidiasis has been reported.
• Systemic dissemination may occur in immunosuppressed patients.
• Candidal esophagitis is a common complication of thrush in immunocompromised patients. In one study, it was the most common opportunistic infection in adults with acquired immunodeficiency syndrome (AIDS) (13.3 episodes per 100 person-years).

Prognosis

• Thrush is considered a self-limited disease, but resolution is hastened by medical therapy.

Patient Education

• Discuss thrush etiology and incidence as part of general reassurance to the parents of the healthy newborn or infant.
• If indicated, offer information about the necessity of further evaluation for underlying immune dysfunction.
• For excellent patient education resources, visit eMedicine's Yeast and Fungal Infections Center. Also, see eMedicine's patient education article Candidiasis (Yeast Infection).

Miscellaneous

Medicolegal Pitfalls

• Serious consideration and determination of the possibility of immune dysfunction is critical for patients beyond infancy, especially those with no apparent underlying cause for thrush (eg, antibiotics, corticosteroids).
• Immunodeficiency should also be considered in the infant with severe thrush associated with failure to thrive, severe eczema, and other infections.

References

1. Hoppe JE. Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J. Sep 1997;16(9):885-94. [Medline].

2. Kalfa VC, Roberts RL, Stiehm ER. The syndrome of chronic mucocutaneous candidiasis with selective antibody deficiency. Ann Allergy Asthma Immunol. Feb 2003;90(2):259-64. [Medline].

3. Liu X, Hua H. Oral manifestation of chronic mucocutaneous candidiasis: seven case reports. J Oral Pathol Med. Oct 2007;36(9):528-32. [Medline].

4. Rowen JL. Mucocutaneous candidiasis. Semin Perinatol. Oct 2003;27(5):406-13. [Medline].

5. Raucher HS. Should we be treating oral thrush?. Pediatr Infect Dis J. Mar 1998;17(3):267. [Medline].

6. [Best Evidence] Adams NP, Bestall JC, Lasserson TJ, et al. Fluticasone versus placebo for chronic asthma in adults and children. Cochrane Database Syst Rev. 2005;CD003135. [Medline].

7. Baley JE. Neonatal candidiasis: the current challenge. Clin Perinatol. Jun 1991;18(2):263-80. [Medline].

8. Brown RS, Berg W, Schlesinger W, Childers EL. The CDx brush biopsy and the diagnosis of oral candidiasis. Dent Today. Aug 2007;26(8):96, 98-9. [Medline].

9. Butler KM, Baker CJ. Candida: an increasingly important pathogen in the nursery. Pediatr Clin North Am. Jun 1988;35(3):543-63. [Medline].

10. Egusa H, Soysa NS, Ellepola AN, Yatani H, Samaranayake LP. Oral candidosis in HIV-infected patients. Curr HIV Res. Nov 2008;6(6):485-99. [Medline].

11. Gonzalez Gravina H, Gonzalez de Moran E, Zambrano O, et al. Oral Candidiasis in children and adolescents with cancer. Identification of Candida spp. Med Oral Patol Oral Cir Bucal. Oct 2007;12(6):E419-23. [Medline].

12. Kumamoto CA, Vinces MD. Alternative Candida albicans lifestyles: growth on surfaces. Annu Rev Microbiol. 2005;59:113-33. [Medline].

13. Kwon-Chung KJ, Bennett JE, eds. Medical Mycology. Philadelphia, Pa: Lea & Febiger; 1992:2288-301.

14. Liguori G, Lucariello A, Colella G, De Luca A, Marinelli P. Rapid identification of Candida species in oral rinse solutions by PCR. J Clin Pathol. Sep 2007;60(9):1035-9. [Medline].

15. Nokta M. Oral manifestations associated with HIV infection. Curr HIV/AIDS Rep. Feb 2008;5(1):5-12. [Medline].

16. Ozturk MA, Gunes T, Koklu E, et al. Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit. Mycoses. Nov 2006;49(6):484-92. [Medline].

17. Pankhurst C. Candidiasis (oropharyngeal). Clin Evid. Jun 2005;1701-16. [Medline].

18. Perniola R, Congedo M, Rizzo A, et al. Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Mycoses. May 2008;51(3):228-35. [Medline].

19. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest. Jul 2004;126(1):213-9. [Medline]. [Full Text].

20. Russell C, Lay KM. Natural history of Candida species and yeasts in the oral cavities of infants. Arch Oral Biol. Aug 1973;18(8):957-62. [Medline].

21. Segal BH, Steinbach WJ. Combination antifungals: an update. Expert Rev Anti Infect Ther. Oct 2007;5(5):883-92. [Medline].

22. Shepherd J. Thrush and breastfeeding. Pract Midwife. Dec 2002;5(11):24-7. [Medline].

23. Su CW, Gaskie S, Jamieson B, Triezenberg D. Clinical inquiries. What is the best treatment for oral thrush in healthy infants?. J Fam Pract. Jul 2008;57(7):484-5. [Medline].

24. Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook. 7^th ed. 2000.

25. Terai H, Shimahara M. Tongue pain: burning mouth syndrome vs Candida- associated lesion. Oral Dis. Jul 2007;13(4):440-2. [Medline].

26. Vazquez JA. Posaconazole for the management of mucosal candidiasis. Future Microbiol. Jun 2007;2:245-56. [Medline].

27. Vazquez JA, Sobel JD. Mucosal candidiasis. Infect Dis Clin North Am. Dec 2002;16(4):793-820, v. [Medline].

Keywords

thrush, Candida albicans, C albicans, candidal diaper rash, candidiasis, diaper dermatitis, fungal infection, hepatosplenomegaly, human immunodeficiency virus, HIV, immune dysfunction, lymphadenopathy, monilia, moniliasis, mucocutaneous candidiasis, oral candidiasis, oral thrush, oropharyngeal yeast infection, polyendocrine disorders, vaginal candidiasis, white tongue coating

Contributor Information and Disclosures

Author

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Coauthor(s)

Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Mudra Kumar, MD, MBBS, MRCP is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital
Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)